1. Field of the Disclosure
The present disclosure relates generally to compounds useful for the inhibition of kinases, and more specifically, to bi-dentate compounds that are useful as kinase inhibitors.
2. Background Information
Protein kinases are families of enzymes that catalyze the phosphorylation of specific residues in proteins, and may be broadly classified into tyrosine or serine/threonine kinases based on the amino acids phosphorylated. This covalent post-translational modification is a pivotal component of normal cellular communication and maintenance of homeostasis.
There is a body of evidence linking kinase misregulation, dysregulation and mutation to a variety of disorders including cancer, diabetes, ocular diseases and other indications. Inappropriate kinase activity triggers a variety of biological cellular responses relating to cell growth, cell differentiation, survival, apoptosis, mitogenesis, cell cycle control, and cell mobility implicated in the above-mentioned and other diseases.
Accordingly, inhibiting kinases, such as C-Jun N-terminal kinase (JNK), is one method of treating various diseases, disorders and pathologies associated with kinases. Previously, some compounds that can be useful as inhibitors of certain kinases, and which target the ATP binding site of the protein, have been identified and synthesized.
While some JNK-interacting peptides (JIP) and JIP mimics capable of doing so have been described previously, no compounds have been reported that are capable of targeting and inhibiting JNK kinase binding to the docking site (JIP site) for the substrate or scaffolding proteins and the ATP binding site at the same time.